Andréia M Leopoldino

• BSc, MS, Ph.D.
• Professor (Associate) at University of São Paulo

Chemoresistance is associated with tumor recurrence, metastases, and short survival. Cisplatin is one of the most used chemotherapies in cancer treatment, including head and neck squamous cell carcinoma (HNSCC), and many patients develop resistance. Here, we established cell lines resistant to cisplatin to better understand epigenetics and biologic...

Bisphenol A (BPA) is an endocrine disrupting chemical able to promote hormone-responsive tumors. The major route of BPA contamination being oral, the aim of the present study was to investigate BPA effects on oral cells. Here, we evaluated the impact of sub-chronic in vivo exposure to BPA and its in vitro effects on neoplastic and non-neoplastic or...

A need exists for further research elucidating the benefits of environmentally safe photoprotective agents against ultraviolet (UV) exposure, and plant extracts represent a human-friendly alternative formulation. This study was designed to evaluate the potential use of Bellis perennis extract (BPE), from the Asteraceae family, known as the common d...

hnRNP K is an important constitutive protein in which is found in the nucleus, cytoplasm, and mitochondria of cells. As such, this protein interacts in turn with various molecules, which are directly involved in gene expression as well as signal transduction. However, it is well-known that its aberrant expression is related to the development of mo...

Galectin-9 (Gal-9) is a beta-galactoside-binding protein with a variety of biological functions related to immune response. However, in allergic diseases, its mechanism of action is not fully understood. This study evaluates the expression pattern of Gal-9 in patients with atopic dermatitis (AD), in ovalbumin (OVA)-induced experimental atopic derma...

In vitro 3D culture models have emerged in the cancer field due to their ability to recapitulate characteristics of the in vivo tumor. Herein, we described the establishment and characterization of 3D multicellular spheroids using ovarian cancer cells (SKOV-3) in co-culture with mesenchymal cells (MUC-9) or fibroblasts (CCD27-Sk). We demonstrated t...

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...

the PDF can be download freely on pubmed. https://pubmed.ncbi.nlm.nih.gov/33634751/

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...

Dehydroepiandrosterone (DHEA) is a steroid hormone secreted by the adrenal glands, gonads and brain. It is a precursor to sex hormones and also is known to have immune modulatory activity. However, little is known about the relationship between DHEA and neutrophils and thus our study evaluates the influence of DHEA in the effector functions of neut...

Non-T cell activation linker (NTAL) is a lipid raft-membrane protein expressed by normal and leukemic cells and involved in cell signaling. In acute promyelocytic leukemia (APL), NTAL depletion from lipid rafts decreases cell viability through regulation of the Akt/PI3K pathway. The role of NTAL in APL cell processes, and its association with clini...

Aim: Histone acetylation and methylation control gene expression. We investigated the impact of SET knockdown on histone methylation status and the consequences for the miRNAs levels in oral squamous cell carcinoma (OSCC). Methods: OSCC cells with and without SET knockdown were analyzed by quantitative real-time PCR to determine miRNA levels, and b...

Herein, a robust docking protocol was developed by using a low-cost workflow to highlight the modulation at ATPase domain from Human Topoisomerase IIα (TOP2A) towards four novels Pd(II)-complexes bearing N, S-donor ligands. In vitro TOP2A inhibition assay confirmed the ability of them to prevent the enzyme functions into concentration ranging at 6....

Lipid rafts are ordered membrane domains, which provide an environment for the proteins participating in signal transduction. Perifosine is an alkylphospholipid (APL) that inhibits the AKT pathway, cytotoxic to neoplastic cells. We have shown that the lipid raft adaptor protein NTAL is a target of APLs in leukemic cells. Using human mantle cell lym...

Molecular alterations in cell death pathways and imbalances in regulators of up- or downstream signaling pathways can lead to resistance to cell death, which is one of the hallmarks of cancer. These signaling modifications are strategies that tumor cells use to resist chemotherapy and that contribute to the high recurrence rate of head and neck squ...

Background A green and efficient synthetic methodology for a wide family of Nacylhydrazones (yields: 42-76%) using microwave irradiation is described, as well as their full characterization. Their potential antineoplastic activity was evaluated in vitro via EMSA by testing protein- DNA interactions. Among the 11 compounds tested, N-acylhydrazone de...

Abstract Mitochondria are central key players in cell metabolism, and mitochondrial DNA (mtDNA) instability has been linked to metabolic changes that contribute to tumorigenesis and to increased expression of pro-tumorigenic genes. Here, we use melanoma cell lines and metastatic melanoma tumors to evaluate the effect of mtDNA alterations and the ex...

The purpose of this contribution is to evaluate the cytotoxicity and apoptosis inducing ability of structurally diverse anthraquinones to establish a relationship between structure and toxicity. Besides the wide spread use of anthraquinones in pharmacological drugs for constipation and non-prescription dietary supplements for weight loss, extracts...

Background: Lymph node metastasis is one of the most important prognostic factors in head and neck squamous cell carcinomas (HNSCCs) and critical for delineating their treatment. However, clinical and histological criteria for the diagnosis of nodal status remain limited. In the present study, we aimed to characterize the proteomic profile of lymp...

Objectives: The objective of this study was to investigate the effects of mate tea (MT) [Ilex paraguariensis] on alveolar socket healing after tooth extraction. Materials and methods: Sixteen male rats were divided into MT and control groups. MT was administered by intragastric gavage at a dose of 20 mg/kg/day for 28 days before and 28 days afte...

Introduction: The study of cancer molecular profiles allowed the development of several targeting agents, such as OP449 and FTY720/Fingolimod drugs, that can act as PP2A activators. OP449 is a synthetic peptide with antineoplastic action and FTY720 is a potent inhibitor of tumor growth and angiogenesis. SET/I2PP2A, a multifunctional protein, is a p...

This study aims to examine the effects of a new 1,4-dihydropyridine derivative, VdiE-2N, on cell signaling pathways and mitochondrial events in head and neck squamous cell carcinoma (HNSCC) cells, and on a mice model of xenograft tumor growth/cell proliferation. Four HNSCC cell lines (HN13, HN12, HN6, and CAL27), HEK293 cells (human embryonic kidne...

Considerable progress has been made on the development of adipose-derived stem/stromal cells (ASCs) as pro-angiogenic therapeutic tools. However, variable clinical results highlight the need for devising strategies to enhance their therapeutic efficacy. Since ASCs proliferate and stabilize newly formed vessels during the angiogenic phase of adipose...

During perimenopause, oxidative stress increases, which may result in disruption of bone turnover, and consequently in osteoporosis. The use of antioxidants may be an effective nutritional approach to reducing osteoporosis in this period of life. Mate tea (MT) (Ilex paraguariensis), a typical and inexpensive beverage consumed in the Brazilian south...

The multifunctional SET/I2PP2A protein is known to be overexpressed in head and neck squamous cell carcinoma. However, SET has been reported to have apparently conflicting roles in promoting cancer cell survival under oxidative stress conditions and preventing invasion and metastasis, complicating efforts to understand the contribution of SET to ca...

The chemokine CCL3 is a chemotactic cytokine crucial for inflammatory cell recruitment in homeostatic and pathological conditions. CCL3 might stimulate cancer progression by promoting leukocyte accumulation, angiogenesis and tumour growth. The expression of CCL3 and its receptors CCR1 and CCR5 was demonstrated in oral squamous cell carcinoma (OSCC)...

Epigenetic modifications are essential in the control of normal cellular processes and cancer development. DNA methylation and histone acetylation are major epigenetic modifications involved in gene transcription and abnormal events driving the oncogenic process. SET protein accumulates in many cancer types, including head and neck squamous cell ca...

Background: MicroRNAs (miRNAs or miRs) are post-transcriptional regulators of eukaryotic cells and knowledge of differences in miR levels may provide new approaches to diagnosis and therapy. Methods: The present study measured the levels of nine miRs in head and neck squamous cell carcinomas (HNSCC) and determined whether clinical pathological feat...

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Dysfunctional clock signaling is observed in a variety of pathological conditions. Many members of the clock gene family are upregulated in tumor cells. Here, we explored the consequences of a commonly disrupted signaling pathway in head and neck cancer on the regulation of circadian clock genes. PTEN is a key molecular controller of the PI3K signa...

This study addressed a potential role of SET/I2PP2A protein on angiogenesis and immune response in head and neck squamous cell carcinoma (HNSCC). A HNSCC cell line with stable SET knockdown (HN12shSET/HN12shControl), previously established in our laboratory, was used to perform (1) qPCR array analysis of genes related to angiogenesis (Qiagen), and...

hnRNP K has been reported to be overexpressed in myeloid leukemia and it is downregulated during retinoic acid (ATRA) induced differentiation of Acute Promyelocytic Leukemia (APL) cells. The aim of the present study was to establish role of hnRNP K in APL using responsive (NB4) and resistant (NB4-R2) cells to the retinoic acid treatment as well as...

The topical administration of chemotherapeutics is a promising approach for the treatment of skin cancer; however, different pharmaceutical strategies are required to allow large amounts of drug to penetrate tumors. This work examined the potential of the anodic iontophoresis of doxorubicin-loaded cationic solid lipid nanoparticles (DOX-SLN) to inc...

Maternal protein restriction in rats increases the risk of adult offspring arterial hypertension through unknown mechanisms. The aims of the study were to evaluate the effects of a low-protein (LP) diet during pregnancy and lactation on baseline sympathetic and respiratory activities and peripheral chemoreflex sensitivity in the rat offspring. Wist...

Introduction: Lipid rafts are highly ordered membrane domains that are enriched in cholesterol and sphingolipids and provide an environment for signal transduction proteins which control cell survival and cell death. Altered raft assembly has been implicated in cancer progression. Alkylphospholipids (APL) inhibit the AKT pathway and induce apoptosi...

Cancer disease is characterized by genomic abnormalities and gene expression aberrations that leads to misregulated activity of apoptosis, angiogenesis and cell proliferation. Heterogeneous ribonucleoprotein K (hnRNP K) is a constitutive protein found in nucleus, cytoplasm and mitochondria of cells and interacts with molecules involved in gene expr...

Heterogeneous ribonucleoprotein K (hnRNP K) is a constitutive protein found in nucleus, cytoplasm and mitochondria of cells and interacts with diverse molecules involved in gene expression and signal transduction. Its over expression is associated with the development of prostate, breast and colorectal cancer types. The binding to nucleotides is th...

SET/I2PP2A is a multifunctional protein that is up-regulated in head and neck squamous cell carcinoma (HNSCC). The action of SET in HNSCC tumorigenicity is unknown. Stable SET knockdown by shRNA (shSET) was established in three HNSCC cell lines: HN12, HN13, and Cal27. Protein expression and phosphorylated protein levels were determined by Western b...

Cisplatin-based chemotherapy is the standard treatment of choice for head and neck squamous cell carcinoma (HNSCC). The efficiency of platinum-based therapies is directly influenced by the development of tumor resistance. Multiple signaling pathways have been linked to tumor resistance, including activation of nuclear factor kappa B (NFκB). We expl...

Lipid rafts are highly ordered membrane domains that are enriched in cholesterol and sphingolipids and provides a scaffold for signal transduction. Altered raft assembly has been implicated in cancer progression. Alkylphospholipids have been used with promising specific cytotoxic effects in different types of cancer cells. These alkylphospholipids...

SET (TAF-1/I2PP2A) is a multifunctional protein that participates in cell cycle control, apoptosis, migration and histone acetylation. It has been reported to be increased in head and neck squamous cell carcinoma (HNSCC) and oral squamous cell carcinoma (OSCC). The participation of SET in the inhibitory complex of histone acetylation contributes to...

Cisplatin-based chemotherapy is the standard treatment of choice for head and neck squamous cell carcinoma (HNSCC). The efficiency of platinum-based therapies is directly influenced by the development of tumor resistance. Multiple signaling pathways have been linked to tumor resistance, including activation of nuclear factor kappa B (NFκB). We expl...

Background: Epigenetic regulation is essential in the control of both normal cellular processes and cancer development. DNA methylation and histone acetylation are involved in chromatin remodeling and gene transcription control. Recently, we reported that SET protein, a member of the acetyltransferase inhibitor complex, is strongly accumulated in H...

Autophagy is a process by which lysosomes degrade and recycle long‐lived proteins and cellular organelles. It degrades cellular components that are worn out/damaged or needed to generate substrates to maintain cellular energy homeostasis under conditions of limited nutrients or stress. Cells of squamous cell cancer of the head and neck (HNSCC), whi...

The prediction of tumor behavior for patients with oral carcinomas remains a challenge for clinicians. The presence of lymph node metastasis is the most important prognostic factor but it is limited in predicting local relapse or survival. This highlights the need for identifying biomarkers that may effectively contribute to prediction of recurrenc...

Partial 2-DE gel images of proteins from “less-aggressive”(T2-3N0) OSCC tumors and surgical margins. Myosin light chain 1/3, skeletal muscle isoform (MLC1/MLC3); annexin A1 (ANXA1); carbonic anhydrase 3 (CA-III); creatine kinase M-type (M-CK); myoglobin (MB); myosin light chain 3 (MYL3); myosin regulatory light chain 2, skeletal muscle isoform (MLC...

Partial 2-DE gel images of proteins from “more-aggressive” (T1-2N+) and “less-aggressive”(T2-3N0) OSCC tumors. Alpha-enolase (ENO1); annexin A2 (ANXA2); cofilin-1 (CFL1); glutathione S-transferase P (GSTP1-1); keratin 19 (CK-19); myoglobin (MB); stratifin (SFN); superoxide dismutase (SOD1). Tumor samples from tongue (C02) and floor of mouth (C04)....

Clinicopathological features of 144 patients with OSCC and techniques used to analyze the samples. T = tumor; Ma = surgical margin; F = female; M = male; P or Neg = positive or negative exposition to tobacco/alcohol, respectively, but consumption time is indeterminate; 1-DE = one-dimensional gel electrophoresis; 2-DE = two-dimensional gel electroph...

Pools organized into groups according to TNM system. 1-DE = one-dimensional gel electrophoresis; 2-DE = two-dimensional gel electrophoresis. (DOC)

Partial 2-DE gel images of proteins from “more-aggressive” (T1-2N+) OSCC tumors and surgical margins. Myosin light chain 1/3, skeletal muscle isoform (MLC1/MLC3); beta-globin (HBB); carbonic anhydrase 3 (CA-III); creatine kinase M-type (M-CK); keratin 4 (CK-4); gamma-actin (ACTG); myoglobin (MB); myosin light chain 3 (MYL3); myosin regulatory light...

Protein identification in “more-aggressive” (MA), “less-aggressive” (LA) tumor groups and their surgical margins (SM) by 1-DE and Scaffold software according to quantitative value. Proteins with a fold change of at least 1.5 were considered with differential abundance between the groups. (PDF)

Differentially expressed proteins identified by 2-DE followed by mass spectrometry analysis in “more-aggressive” (MA), “less-aggressive” (LA) tumor groups and their surgical margins (SM). MA/SM, LA/SM and MA/LA abundance ratio. (DOC)

Lipid rafts are highly ordered membrane domains rich in cholesterol and sphingolipids that provide a scaffold for signal transduction proteins; altered raft structure has also been implicated in cancer progression. We have shown that 25 μm 10-(octyloxy) decyl-2-(trimethylammonium) ethyl phosphate (ODPC), an alkylphospholipid, targets high cholester...

Alcohol and tobacco consumption are risk factors for head and neck squamous cell carcinoma (HNSCC). Aldehyde dehydrogenase 2 (ALDH2) and glutathione S-transferase pi 1 (GSTP1) are important enzymes for cellular detoxification and low efficiencies implicates in cancer. We assessed potential role of the SET protein overexpression, a histone acetylati...

Human N-myc downstream-regulated gene 1 (NDRG1) is a metastasis suppressor gene with several potential functions, including cell differentiation, cell cycle regulation and response to hormones, nickel and stress. The purpose of this study was to investigate the immunoexpression of NDRG1 in oral and oropharyngeal squamous cell carcinomas searching f...

Oxidative stress and mitochondrial impairment are essential in the ischemic stroke cascade and eventually lead to tissue injury. C-Phycocyanin (C-PC) has previously been shown to have strong antioxidant and neuroprotective actions. In the present study, we assessed the effects of C-PC on oxidative injury induced by tert-butylhydroperoxide (t-BOOH)...

Determination of the SET protein levels in head and neck squamous cell carcinoma (HNSCC) tissue samples and the SET role in cell survival and response to oxidative stress in HNSCC cell lineages. SET protein was analyzed in 372 HNSCC tissue samples by immunohistochemistry using tissue microarray and HNSCC cell lineages. Oxidative stress was induced...

Poor pharmacokinetics and toxicity are responsible for most drug candidate failures. In order to attempt to some degree of ADMET (Absorption, Distribution, Metabolism, Excrection and Toxicity) information, in silico predictions arise currently as an interesting alternative to evaluate prototypes during early stages of the drug design processes, esp...

SET protein (I2PP2A) is an inhibitor of PP2A, which regulates the phosphorylated Akt (protein kinase B) levels. We assessed the effects of SET overexpression in HEK293T cells, both in the presence and the absence of mild oxidative stress induced by 50 μM tert-butyl hydroperoxide. Immunoblotting assays demonstrated that SET accumulated in HEK293T ce...

Up-regulation of S100A7 (Psoriasin), a small calcium-binding protein, is associated with the development of several types of carcinomas, but its function and possibility to serve as a diagnostic or prognostic marker have not been fully defined. In order to prepare antibodies to the protein for immunohistochemical studies we produced the recombinant...

Guttiferone-A (GA) is a natural occurring polyisoprenylated benzophenone with cytotoxic action in vitro and anti-tumor action in rodent models. We addressed a potential involvement of mitochondria in GA toxicity (1-25 μM) toward cancer cells by employing both hepatic carcinoma (HepG2) cells and succinate-energized mitochondria, isolated from rat li...

Nemorosone, a natural-occurring polycyclic polyprenylated acylphloroglucinol, has received increasing attention due to its strong in vitro anti-cancer action. Here, we have demonstrated the toxic effect of nemorosone (1-25 μM) on HepG2 cells by means of the MTT assay, as well as early mitochondrial membrane potential dissipation and ATP depletion i...

Genetic variation in immune response is probably involved in the progression of sepsis and mortality in septic patients. However, findings in the literature are sometimes conflicting or their significance is uncertain. Thus, we investigated the possible association between 12 polymorphisms located in the interleukin-6 (IL6), IL10, TLR-2, Toll-like...

The development and progression of cancer depend on its genetic characteristics as well as on the interactions with its microenvironment. Understanding these interactions may contribute to diagnostic and prognostic evaluations and to the development of new cancer therapies. Aiming to investigate potential mechanisms by which the tumor microenvironm...

Annexin A1 (ANXA1) is a soluble cytoplasmic protein, moving to membranes when calcium levels are elevated. ANXA1 has also been shown to move to the nucleus or outside the cells, depending on tyrosine-kinase signalling, thus interfering in cytoskeletal organization and cell differentiation, mostly in inflammatory and neoplastic processes. The aim wa...

Oral squamous cell carcinoma (OSCC) is a frequent neoplasm, which is usually aggressive and has unpredictable biological behavior and unfavorable prognosis. The comprehension of the molecular basis of this variability should lead to the development of targeted therapies as well as to improvements in specificity and sensitivity of diagnosis. Samples...

The heterogeneous nuclear ribonucleoproteins (hnRNPs) comprise a large family of proteins that play important roles in telomere biogenesis, DNA repair, cellular signaling, and the regulation of expression at both the transcriptional and translational levels. One of the most extensively studied hnRNP family members, hnRNP K, has been implicated in a...

The human cyclin-dependent kinase 9 (CDK9) protein was expressed in E. coli BL21 using the pET23a vector at 30 degrees C. Several milligrams of protein were purified from soluble fraction using ionic exchange and ATP-affinity chromatography. The structural quality of recombinant CDK9 and the estimation of its secondary structure were obtained by ci...

In the present study, we compared six different solubilization buffers and optimized two-dimensional electrophoresis (2-DE) conditions for human lymph node proteins. In addition, we developed a simple protocol for 2-D gel storage. Efficient solubilization was obtained with lysis buffers containing (a) 8 M urea, 4% CHAPS (3-[(3-cholamidopropyl) dime...

The present work reports the characterization of Fastuosain, a novel cysteine protease of 25kDa, purified from the unripe fruits of Bromelia fastuosa, a wild South American Bromeliaceae. Proteolytic activity, measured using casein and synthetic substrates, was dependent on the presence of thiol reagents, having maximum activity at pH 7.0. The prese...

The present work reports the characterization of Fastuosain, a novel cysteine protease of 25kDa, purified from the unripe fruits of Bromelia fastuosa, a wild South American Bromeliaceae. Proteolytic activity, measured using casein and synthetic substrates, was dependent on the presence of thiol reagents, having maximum activity at pH 7.0. The prese...